This proposal is concerned with the control of DNA synthesis in normal rat liver mitochondria in vitro by soluble cytoplasmic factor(s) from actively dividing tissues such as solid rodent neoplasms and regenerating liver. Such factors have been demonstrated in the 15-hr, 105,000 x g post microsomal supernatant fluid from rat hepatoma 7777, rat Walker R256 mammary carcinosarcoma, mouse Gardner lymphoma and 22-hr regenerating rat liver but not in normal rat liver supernatant. The active factor(s) which is heat stable, non dialyzable, precipitated by ammonium sulfate and insensitive to DNase and RNase will be purified from rat hepatoma and/or 22-hr regenerating liver and characterized and the mechanism by which the cytoplasmic factor "turns on" mitochondrial DNA synthesis will be investigated.